Clozapine Antimuscarinics

Figure 17.5 Possible scheme for the initiation of depolarisation block of DA neurons. In (a) the excitatory effect of glutamate released on to the DA neuron from the afferent input is counteracted by the inhibitory effect of DA, presumed to be released from dendrites, acting on D2 autoreceptors. In the absence of such inhibition due to the presence of a typical neuroleptic (b) the neuron will fire more frequently and eventually become depolarised. At5q)ical neuroleptics, like clozapine, will be less likely to produce the depolarisation of A9 neurons because they are generally weaker D2 antagonists and so will reduce the DA inhibition much less allowing it to counteract the excitatory input. Additionally some of them have antimuscarinic activity and will block the excitatory effect of ACh released from intrinsic neurons (see Fig. 17.7)...

The case in context Clozapine is a newer antipsychotic that can, like other agents in its class, produce antimuscarinic side effects. Although Ms. Doe had not complained of anticholinergic effects prior to beginning treatment with a moderate dose of diphenhydramine, it is likely that the additive anticholinergic effects of clozapine and diphenhydramine resulted in urinary retention. 

NITRATES 1. ANALGESICS-nefopam 2. ANTIARRHYTHMICS -disopyramide, propafenone 3. ANTIDEPRESSANTS-TCAs 4. ANTI EMETICS-cydizine 5. ANTIHISTAMINES -chlorphenamine, cyproheptadine, hydroxyzine 6. ANTIMUSCARINICS -atropine, benzatropine, cydopentolate, dicydover-ine, flavoxate, homat-ropine, hyoscine, orphenadrine, oxybutynin, procyclidine, propantheline, tolterodine, trihexyphenidyl, tropicamide. 7. ANTI-PARKINSON S DRUGS-dopaminergics 8. ANTI-PSYCHOTICS - pheno-thiazines, clozapine, pimozide 9. MUSCLE RELAXANTS-baclofen 1. t risk of antimuscarinic side-effects when isosorbide dinitrate is co-administered with these drugs 2. 1 efficacy of sublingual nitrate tablets... 

ANTIPSYCHOTICS-PHENOTHIAZINE, CLOZAPINE, PIMOZIDE NITRATES 1. T risk of antimuscarinic side-effects when isosorbide dinitrate is co administered with these drugs. 2.1 efficacy of sublingual nitrate tablets 1. Additive effect both of these drugs cause antimuscarinic side-effects 2. Antimuscarinic effects i saliva production, which i dissolution of the tablet 1. Warn patient of these effects 2. Consider changing the formulation to a sublingual nitrate spray... 

The antimuscarinic action of clozapine and thioridazine can cause tachycardia and enhance the peripheral and central effects (confusion, delirium) of other anticholinergic agents, such as the tricyclic antidepressants and antiparkinson agents. 

ANTIMUSCARINICS-atropine, benzatropine, cyclopentolate, dicyclover-ine, flavoxate, homa-tropine, hyoscine, orphenadrine, oxybutynin, procyclidine, propantheline, tolterodine, trihexyphenidyl, tropicamide 7. ANTI-PARKINSON S DRUGS-dopaminergics 8. ANTI-PSYCHOTICS - pheno-thiazines, clozapine, pimozide 9. MUSCLE RELAXANTS - baclofen... 

The antimuscariiiic effects of clozapine are additive with those of other antimuscarinic drugs, which has led to urinary retention and delirium. 

The manufacturers of clozapine warn that the antimuscarinic effects of some drugs may be additive with those of clozapine, which may lead to adverse effects such as dry mouth and constipation. Confirmation ofthe clinical relevance of this proposed interaction was seen in a patient who developed severe urinary retention while taking clozapine and mecloz-ine. ... 

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